Beeby Morgan, O'Connor Brian D, Ryttersgaard Carsten, Boutz Daniel R, Perry L Jeanne, Yeates Todd O
UCLA-DOE Institute for Genomics and Proteomics, University of California, Los Angeles, California, USA.
PLoS Biol. 2005 Sep;3(9):e309. doi: 10.1371/journal.pbio.0030309. Epub 2005 Aug 23.
Thermophilic organisms flourish in varied high-temperature environmental niches that are deadly to other organisms. Recently, genomic evidence has implicated a critical role for disulfide bonds in the structural stabilization of intracellular proteins from certain of these organisms, contrary to the conventional view that structural disulfide bonds are exclusively extracellular. Here both computational and structural data are presented to explore the occurrence of disulfide bonds as a protein-stabilization method across many thermophilic prokaryotes. Based on computational studies, disulfide-bond richness is found to be widespread, with thermophiles containing the highest levels. Interestingly, only a distinct subset of thermophiles exhibit this property. A computational search for proteins matching this target phylogenetic profile singles out a specific protein, known as protein disulfide oxidoreductase, as a potential key player in thermophilic intracellular disulfide-bond formation. Finally, biochemical support in the form of a new crystal structure of a thermophilic protein with three disulfide bonds is presented together with a survey of known structures from the literature. Together, the results provide insight into biochemical specialization and the diversity of methods employed by organisms to stabilize their proteins in exotic environments. The findings also motivate continued efforts to sequence genomes from divergent organisms.
嗜热生物在各种高温环境生态位中蓬勃发展，而这些环境对其他生物来说是致命的。最近，基因组证据表明二硫键在其中某些生物的细胞内蛋白质结构稳定中起关键作用，这与结构二硫键仅存在于细胞外的传统观点相反。本文展示了计算和结构数据，以探索二硫键作为一种蛋白质稳定化方法在众多嗜热原核生物中的存在情况。基于计算研究，发现二硫键丰富度很普遍，嗜热菌中的水平最高。有趣的是，只有一小部分独特的嗜热菌表现出这种特性。对符合该目标系统发育谱的蛋白质进行计算搜索，筛选出一种特定的蛋白质，即蛋白质二硫键氧化还原酶，作为嗜热细胞内二硫键形成的潜在关键参与者。最后，展示了一种具有三个二硫键的嗜热蛋白质新晶体结构形式的生化支持以及对文献中已知结构的综述。这些结果共同提供了对生物化学特化以及生物体在特殊环境中稳定其蛋白质所采用方法多样性的见解。这些发现也促使人们继续努力对不同生物的基因组进行测序。
